Trypanosomiasis which is induced by trypanosome protozoa is classified broadly into two groups, depending on the species of disease-causing parasites. The first group is African trypanosomiasis (African sleeping sickness) parasite of which is Trypanosoma brucei, which is further subdivided to Trypanosoma brucei gambiense, and Trypanosoma brucei rhodesiense. The second group is American trypanosomiasis (Chagas's disease) parasite of which is Trypanosoma cruzi. These protozoa infect not only human but various animals including dogs, cats, horses and cows. Therefore, it is concerned that infection of trypanosomiasis would be distributed around the world.
African trypanosomiasis-infected humans are observed throughout African continent, and it is estimated that there are approximately 60 millions of patients. Specifically, Trypanosoma brucei gambiense is observed in West and Central Africa, and Trypanosoma brucei rhodesiense is observed in East and South Africa. African trypanosomiasis is mediated by tsetse flies and is sometimes spread explosively where public hygiene is belated. Protozoa invades from the tsetse fly-bited site into blood flow or lymph nodes, inducing intermittent fever, headaches, ague, and transient edema. Later, when the central nervous system is invaded by protozoa, continuous headaches, somnolence during daylight, ataxio and coma appear, and finally leads the patient to death in several months to several years.
Agents for treating African trypanosomiasis are not satisfactory, and all of the agents require hospital admission and a long period administration. These agents are expensive, and often have harmful side-effects. For example, pentamidine which is used in the primary treatment is required to be administered at high doses by several intravenous or muscular injections within 3 weeks, which causes physical and economic burden. For central nervous systems diseases, melarsoprol, which is an agent containing arsenicum, is used. However, as it requires continuous administration for several weeks, side-effects lead by arsenic toxicity is inevitable. African trypanosomiasis is a life-threatening disease when left untreated, and development of a novel chemotherapeutic drug is awaited. Further, livestock including bovines and horses are infected by trypanosomiasis which result in death. Outbreaks often occur in Africa in livestock, which cause significant economic loss (for example, see Hoet, S. et al., Natural Product Reports, 2004, vol. 21, pp. 353-364).
Human infection of American trypanosomiasis (Shaga's disease) is reported mainly in many states in the United States, and throughout Central and South America. The total number of patients is roughly estimated to be approximately 20 millions. Mediating-insect of American trypanosomiasis is an insect relatively large called Reduviidae. When a person starches an itching site of a Reduviidae-bite, protozoa invade from Reduviidae feces and inoculate into blood flow or lymph nodes. Symptoms include fever, anthema, blepharedema, lymphadenitis, myocarditis, meningoencephalitis, and some cases are led to death within 2 to 4 weeks. Adults usually follow a chronic course, while children often exhibit acute symptoms and the fatality is said to be high. Benznidazole is used for treating American trypanosomiasis. However, it is only effective for early stage of infection, and requires to be administered continuously for 1 to 4 months. Further, carcinogenicity effect is reported. Therefore, as there is no effective drugs for American trypanosomiasis, World Health Organization (WHO) alerts that development of chemotherapeutic agents is necessary (for example, see Teixeira, M. M. et al., Trends Parasitology, 2002, vol. 18, pp. 262-268).
On the other hand, rhodacyanine pigments which are used in the present invention are known to be effective for treating tumors (for example, see Japanese Laid-Open Patent Application No. 5-117148). Further, the present inventors have proposed that rhodacyanine pigments show an anti-malarial activity (for example, see Japanese Laid-Open Patent Application No. 2000-191531; Japanese Laid-Open Patent Application No. 2003-034640; Japanese Laid-Open Patent Application No. 2003-034641; Japanese Laid-Open Patent Application No. 2003-034642).
Patent document 1: Japanese Laid-Open Patent Application No. 5-117148
Patent document 2: Japanese Laid-Open Patent Application No. 2000-191531
Patent document 3: Japanese Laid-Open Patent Application No. 2003-034640
Patent document 4: Japanese Laid-Open Patent Application No. 2003-034641
Patent document 5: Japanese Laid-Open Patent Application No. 2003-034642
Non-patent document 1: Hoet, S. et al., Natural Product Reports, 2004, vol. 21, pp. 353-364
Non-patent document 2: Teixeira, M. M. et al., Trends Parasitology, 2002, vol. 18, pp. 262-268